Method for debrominating 9-halogenated steroid compounds and applications thereof

Abstract

The present invention provides a method for dehalogenating 9-halogenated steroid compounds and its application, which relates to the technical field of chemical synthesis. The method for dehalogenating 9-halogenated steroid compounds includes the following steps: Compound I reacts with a thiofatty acid salt to obtain the 9-dehalogenated product Compound II of the 9-halogenated steroid compound. The method for dehalogenating 9-halogenated steroid compounds provided by the present invention reacts Compound I with a thiofatty acid salt to obtain the 9-dehalogenated product Compound II of the 9-halogenated steroid compound. Toxic reagents such as zinc powder, chromium granules or tri-n-butyltin, which are highly toxic and cause serious environmental pollution, are not used in the reaction. It is green and environmentally friendly, the synthesis process is simple and easy to operate, and the production applicability is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and particularly relates to a method for dehalogenating 9-halogenated steroid compounds and its application. Background Art

[0002] Steroid hormone drugs refer to hormone drugs with a steroid structure in their molecular structure. They are widely used clinically and mainly include two categories: adrenal cortical hormones and sex hormones. Among them, adrenal cortical hormones have various pharmacological effects such as anti-inflammatory, anti-allergic, immunosuppressive, enhancing stress response, anti-endotoxin, and anti-shock. Clinically, they can be used to treat many diseases and are an important class of drugs indispensable in clinical practice.

[0003] In the synthesis of many corticosteroid drugs, it is necessary to carry out a reduction dehalogenation reaction on the halogen at the 9-position. Commonly used reducing agents in industry include zinc powder, chromium grains, or tri-n-butyltin, etc.

[0004] Currently, the most commonly used is zinc powder.

[0005] J.Chem.Soc.PerkinTrans.1,1986:1621 and patent CN106866765A reported that 9-bromo-11-carbonyl steroid compounds were added to a zinc powder / acetic acid suspension and stirred at room temperature to obtain 11-carbonyl steroid compounds.

[0006] Most of the above processes use heavy metal raw materials, raw materials with high toxicity, etc., causing serious environmental pollution, high environmental protection treatment costs, or the use of restricted raw materials; thus, it limits the normal application of such reactions and affects the normal production of such products.

[0007] In view of this, the present invention is specifically proposed. Summary of the Invention

[0008] The main object of the present invention is to provide a method for dehalogenating 9-halogenated steroid compounds and its application, in order to at least partially solve at least one of the above technical problems. As the first aspect of the present invention, the present invention provides a method for dehalogenating 9-halogenated steroid compounds, including the following steps: Compound I reacts with a thiofatty acid salt to obtain a 9-position dehalogenated product Compound II of the 9-halogenated steroid compound, and the reaction formula is as follows:

[0009]

[0010] Among them, R1, R2, R3, and R4 shown in the structural formulas of Compound I and Compound II are independently selected from each other, and:

[0011] R1 = H or methyl;

[0012] R2 = H, OH or methyl; R3 = H, OH, R5, OR5, OCOR5 or OCOOR5, where R5 is an alkyl group with six or fewer carbon atoms;

[0013] or, R2, i.e., there is also an oxygen bridge connecting between C16 and C17, and R6 and R7 are independently H or an alkyl group with six or fewer carbon atoms;

[0014] or, R2, i.e., there is also an epoxy group connecting between C16 and C17;

[0015] or, R2, R3 = single bond, i.e., there is also a double bond connecting between C16 and C17;

[0016] R4 = CH2R8, R8 = H, OH or OCOR9, where R9 is an alkyl group with six or fewer carbon atoms;

[0017] X = Cl, Br or I;

[0018] The dotted line is a single bond or a double bond.

[0019] The method for dehalogenating 9-halogenated steroid compounds provided by the present invention obtains the 9-dehalogenated product compound II of 9-halogenated steroid compounds by reacting compound I with thiofatty acid salts. In the reaction, no reagents with high toxicity and serious environmental pollution such as zinc powder, chromium grains or tri-n-butyltin are used. It is green and environmentally friendly, the synthesis process is simple and easy to operate, and the production applicability is improved.

[0020] Furthermore, it includes the following steps: Compound I reacts with thiofatty acid salts to obtain the 9-dehalogenated product compound II of 9-halogenated steroid compounds. The reaction formula is as follows:

[0021]

[0022] Among them, R1, R2, R3 and R4 shown in the structural formulas of compound I and compound II are independently selected, and:

[0023] R1 = H or methyl;

[0024] R2 = H or methyl; R3 = H or OH;

[0025] or, R2, i.e., there is also an oxygen bridge connecting between C16 and C17, and R6 and R7 are independently H or an alkyl group with six or fewer carbon atoms;

[0026] or, R2, i.e., there is also an epoxy group connecting between C16 and C17;

[0027] Or, R2, R3 = single bond, i.e., there is also a double bond between C16 and C17 positions;

[0028] R4 = CH2R8, R8 = H, OH or OCOR9, and R9 is an alkyl group with six or fewer carbon atoms;

[0029] X = Cl, Br;

[0030] The dotted line represents a single bond or a double bond.

[0031] Furthermore, it includes the following steps: Compound I reacts with thiofatty acid salt to obtain the 9 - dehalogenated product Compound II of 9 - halogenated steroid compound, and the reaction formula is as follows:

[0032]

[0033] Among them, R1, R2, R3, and R4 shown in the structural formulas of Compound I and Compound II are independently selected from each other, and:

[0034] R1 = H;

[0035] R2 = H or methyl; R3 = H or OH;

[0036] R4 = CH2R8, R8 = H or OCOCH3;

[0037] X = Br;

[0038] The dotted line represents a single bond or a double bond.

[0039] Furthermore, the thiofatty acid salt is selected from one or a combination of several of thioacetate, thiopropionate or thiobutyrate.

[0040] Furthermore, the thioacetate is selected from sodium thioacetate and / or potassium thioacetate;

[0041] And / or, the thiopropionate is selected from sodium thiopropionate and / or potassium thiopropionate;

[0042] And / or, the thiobutyrate is selected from sodium thiobutyrate and / or potassium thiobutyrate.

[0043] Furthermore, the molar ratio of the thiofatty acid salt to Compound I in the reaction is (1.2 - 2):1.

[0044] In the present invention, typical but non - limiting molar ratios of thioacetate to Compound I can be, for example, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1 or 2.0:1.

[0045] Further, it includes the following steps: adding compound I and thioacetate into a solvent, reacting at 30 - 80 °C to obtain compound II, which is the 9-dehalogenated product of the 9-halogenated steroid compound.

[0046] In the present invention, the typical but non-limiting temperature of the reaction can be, for example, 30 °C, 32 °C, 34 °C, 36 °C, 38 °C, 40 °C, 42 °C, 44 °C, 46 °C, 48 °C, 50 °C, 52 °C, 54 °C, 56 °C, 58 °C, 60 °C, 62 °C, 64 °C, 66 °C, 68 °C, 70 °C, 72 °C, 74 °C, 76 °C, 78 °C or 80 °C.

[0047] The dehalogenation method of the 9-halogenated steroid compound provided by the present invention does not use highly toxic and high-risk chemical reagents, the reaction conditions are mild, the reaction can be completed at 30 - 80 °C, it has strong operability, a high safety factor, and improves the production applicability.

[0048] Further, the solvent is selected from one or a combination of several of C1-C4 alcohols, acetonitrile or N,N-dimethylformamide.

[0049] Further, the C1-C4 alcohols are selected from methanol, ethanol, isopropanol or n-butanol.

[0050] Further, the volume-weight ratio of the solvent to compound I is (3 - 6) mL / g.

[0051] In the present invention, the typical but non-limiting volume-weight ratio of the solvent to compound I can be, for example, 3 mL / g, 3.5 mL / g, 4 mL / g, 4.5 mL / g, 5 mL / g, 5.5 mL / g or 6 mL / g.

[0052] As the second aspect of the present invention, the present invention provides the application of the above dehalogenation method of the 9-halogenated steroid compound in the preparation of corticosteroid drugs and their intermediates.

[0053] The present invention uses the dehalogenation method of the 9-halogenated steroid compound to prepare corticosteroid drugs and their intermediates. In the synthesis route, chemical reagents with high toxicity and serious environmental pollution are avoided, it has strong operability, a high safety factor, and improves the production applicability.

[0054] Further, the corticosteroid drugs include cortisone, cortisone acetate, prednisone, methylprednisone, methylprednisone acetate.

[0055] The corticosteroid drugs in the present invention include but are not limited to the above drugs.

[0056] Compared with the prior art, the present invention has the following beneficial effects:

[0057] (1) The dehalogenation method of 9-halogenated steroid compounds provided by the present invention obtains the 9-position dehalogenated product compound II of 9-halogenated steroid compounds by reacting compound I with thiofatty acid salts. In the reaction, no reagents with high toxicity such as zinc powder, chromium particles or tri-n-butyltin, which cause serious environmental pollution, are used. It is green and environmentally friendly, the synthesis process is simple and easy to operate, and the production applicability is improved.

[0058] (2) The present invention applies the dehalogenation method of 9-halogenated steroid compounds to the preparation of corticosteroid drugs and their intermediates. Toxic chemical reagents with high toxicity and serious environmental pollution are avoided in the synthesis route. It has strong operability, high safety factor, and improves production applicability. Detailed implementation mode

[0059] The following will describe the implementation scheme of the present invention in detail with reference to the examples. However, those skilled in the art will understand that the following examples are only used to illustrate the present invention and should not be regarded as limiting the scope of the present invention. For those not specified in the examples, the conventional conditions are followed. For reagents or instruments not specified by the manufacturer, they are all conventional products that can be obtained through commercial purchase.

[0060] Example 1

[0061]

[0062] Example 1-1

[0063] At room temperature, 10 g of compound I-1, 3.4 g of potassium thioacetate and 50 mL of ethanol were added to a reaction flask, heated to 70 °C for reaction, monitored by TLC until there was no compound I-1. After the reaction was completed, the reaction solution was concentrated, water was added, and it was continuously concentrated until no solvent was distilled out. The concentrate was diluted in 10 times the amount of water, stirred for 30 min, filtered, discharged, dried, and 7.7 g of compound II-1 was obtained, with a yield of 95.7% and an HPLC purity of 98.2%.

[0064] Example 1-2

[0065] At room temperature, 10 g of compound I-1, 3.9 g of sodium thioacetate and 60 mL of N,N-dimethylformamide were added to a reaction flask, heated to 80 °C for reaction, monitored by TLC until there was no compound I-1. After the reaction was completed, it was diluted in 30 times the amount of water, stirred for 30 min, filtered, discharged, dried, and 7.6 g of compound II-1 was obtained, with a yield of 95.5% and a purity of 98.0%.

[0066] Example 1-3

[0067] At room temperature, 10 g of Compound I-1, 2.7 g of potassium thioacetate and 30 mL of acetonitrile were added to a reaction flask, and the temperature was raised to 30 °C for reaction. The reaction was monitored by TLC until there was no Compound I-1 left. After the reaction was completed, the reaction solution was concentrated, water was added, and the concentration was continued until no solvent was distilled out. The concentrate was diluted in 10 times the amount of water, stirred for 30 min, filtered by suction, discharged, and dried to obtain 6.5 g of Compound II-1, with a yield of 80.4% and a purity of 96.8%.

[0068] Example 2

[0069]

[0070] Example 2-1

[0071] At room temperature, 10 g of Compound I-2, 3.5 g of sodium thioacetate and 40 mL of acetonitrile were added to a reaction flask, and the temperature was raised to 60 °C for reaction. The reaction was monitored by TLC until there was no Compound I-2 left. After the reaction was completed, the reaction solution was concentrated, water was added, and the concentration was continued until no solvent was distilled out. The concentrate was diluted in 10 times the amount of water, stirred for 30 min, filtered by suction, discharged, and dried to obtain 7.4 g of Compound II-2, with a yield of 91.9% and a purity of 97.8%.

[0072] Example 2-2

[0073] At room temperature, 10 g of Compound I-2, 5.2 g of potassium thiopropionate and 30 mL of methanol were added to a reaction flask, and the temperature was raised to 30 °C for reaction. The reaction was monitored by TLC until there was no Compound I-2 left. After the reaction was completed, the reaction solution was concentrated, water was added, and the concentration was continued until no solvent was distilled out. The concentrate was diluted in 10 times the amount of water, stirred for 30 min, filtered by suction, discharged, and dried to obtain 6.5 g of Compound II-2, with a yield of 80.7% and a purity of 97.1%.

[0074] Example 2-3

[0075] At room temperature, 10 g of Compound I-2, 2.7 g of sodium thiopropionate and 60 mL of N,N-dimethylformamide were added to a reaction flask, and the temperature was raised to 80 °C for reaction. The reaction was monitored by TLC until there was no Compound I-2 left. After the reaction was completed, it was diluted in 30 times the amount of water, stirred for 30 min, filtered by suction, discharged, and dried to obtain 7.5 g of Compound II-2, with a yield of 93.9% and a purity of 97.4%.

[0076] Example 3

[0077]

[0078] Example 3-1

[0079] At room temperature, 10 g of Compound I-3, 3.9 g of potassium thioacetate and 40 mL of isopropanol were added to a reaction flask, and the temperature was raised to 40 °C for reaction. The reaction was monitored by TLC until there was no Compound I-3. After the reaction was completed, the reaction solution was concentrated, water was added, the concentrate was diluted in 30 times the amount of water, stirred for 30 min, filtered by suction, discharged, and dried to obtain 7.0 g of Compound II-3 with a yield of 84.6% and a purity of 97.9%.

[0080] Example 3-2

[0081] At room temperature, 10 g of Compound I-3, 5.8 g of potassium thiobutyrate and 30 mL of N,N-dimethylformamide were added to a reaction flask, and the temperature was raised to 80 °C for reaction. The reaction was monitored by TLC until there was no Compound I-3. After the reaction was completed, it was diluted in 30 times the amount of water, stirred for 30 min, filtered by suction, discharged, and dried to obtain 7.8 g of Compound II-3 with a yield of 93.7% and a purity of 98.2%.

[0082] Example 3-3

[0083] At room temperature, 10 g of Compound I-3, 3.1 g of potassium thiopropionate and 60 mL of ethanol were added to a reaction flask, and the temperature was raised to 30 °C for reaction. The reaction was monitored by TLC until there was no Compound I-3. After the reaction was completed, the reaction solution was concentrated, water was added, and it was continuously concentrated until no solvent was distilled out. The concentrate was diluted in 10 times the amount of water, stirred for 30 min, filtered by suction, discharged, and dried to obtain 6.5 g of Compound II-3 with a yield of 78.6% and a purity of 96.9%.

[0084] Example 4

[0085]

[0086] Example 4-1

[0087] At room temperature, 10 g of Compound I-4, 5.7 g of potassium thioacetate and 50 mL of acetonitrile were added to a reaction flask, and the temperature was raised to 50 °C for reaction. The reaction was monitored by TLC until there was no Compound I-4. After the reaction was completed, the reaction solution was concentrated, water was added, and it was continuously concentrated until no solvent was distilled out. The concentrate was diluted in 10 times the amount of water, stirred for 30 min, filtered by suction, discharged, and dried to obtain 7.5 g of Compound II-4 with a yield of 91.0% and a purity of 98.2%.

[0088] Example 4-2

[0089] At room temperature, 10 g of Compound I-4, 3.0 g of sodium thioacetate and 30 mL of n-butanol were added to a reaction flask, and the temperature was raised to 80 °C for reaction. The reaction was monitored by TLC until there was no Compound I-4. After the reaction was completed, it was diluted in 30 times the amount of water, stirred for 30 min, filtered by suction, discharged, and dried to obtain 7.6 g of Compound II-4 with a yield of 92.3% and a purity of 97.7%.

[0090] Example 4-3

[0091] At room temperature, 10 g of Compound I-4, 4.4 g of sodium thiobutyrate and 60 mL of methanol were added to a reaction flask, and the temperature was raised to 30 °C for reaction. The reaction was monitored by TLC until there was no Compound I-4. After the reaction was completed, the reaction solution was concentrated, water was added, and the concentration was continued until no solvent was distilled out. The concentrate was diluted in 10-fold water, stirred for 30 min, filtered by suction, discharged, dried, and 6.7 g of Compound II-4 was obtained, with a yield of 81.2% and a purity of 97.2%.

[0092] Example 5

[0093]

[0094] At room temperature, 10 g of Compound I-5, 3.6 g of sodium thiobutyrate and 60 mL of N,N-dimethylformamide were added to a reaction flask, and the reaction was carried out at 80 °C. The reaction was monitored by TLC until there was no Compound I-5. After the reaction was completed, it was diluted in 30-fold water, stirred for 30 min, filtered by suction, discharged, dried, and 7.7 g of Compound II-5 was obtained, with a yield of 93.2% and a purity of 98.2%.

[0095] Example 6

[0096]

[0097] At room temperature, 10 g of Compound I-6, 4.0 g of sodium thioacetate and 60 mL of acetonitrile were added to a reaction flask, and the reaction was carried out at 30 °C. The reaction was monitored by TLC until there was no Compound I-6. The reaction solution was concentrated, water was added, and the concentration was continued until no solvent was distilled out. The concentrate was diluted in 10-fold water, stirred for 30 min, filtered by suction, discharged, dried, and 6.8 g of Compound II-6 was obtained, with a yield of 81.2% and a purity of 96.7%.

[0098] Example 7

[0099]

[0100] At room temperature, 10 g of Compound I-7, 3.4 g of sodium thiopropionate and 40 mL of isopropanol were added to a reaction flask, and the temperature was raised to 70 °C for reaction. The reaction was monitored by TLC until there was no Compound I-7. After the reaction was completed, the reaction solution was concentrated, water was added, and the concentration was continued until no solvent was distilled out. The concentrate was diluted in 10-fold water, stirred for 30 min, filtered by suction, discharged, dried, and 8.7 g of Compound II-7 was obtained, with a yield of 93.1% and a purity of 98.2%.

[0101] Example 8

[0102]

[0103] At room temperature, 10 g of Compound I-8, 4.0 g of potassium thioacetate, and 40 mL of n-butanol were added to a reaction flask. The temperature was raised to 80 °C for reaction. TLC was used to monitor until there was no Compound I-8. After the reaction was completed, it was diluted in 30 times the amount of water, stirred for 30 min, filtered by suction, discharged, and dried to obtain 7.6 g of Compound II-8, with a yield of 92.1% and a purity of 97.9%.

[0104] Example 9

[0105]

[0106] At room temperature, 10 g of Compound I-9, 4.2 g of sodium thioacetate, and 30 mL of acetonitrile were added to a reaction flask. The temperature was raised to 50 °C for reaction. TLC was used to monitor until there was no Compound I-9. After the reaction was completed, the reaction solution was concentrated, water was added, and it was continuously concentrated until no solvent was distilled out. The concentrate was diluted in 10 times the amount of water, stirred for 30 min, filtered by suction, discharged, and dried to obtain 7.9 g of Compound II-9, with a yield of 87.3% and a purity of 96.6%.

[0107] Example 10

[0108]

[0109] At room temperature, 10 g of Compound I-10, 3.6 g of sodium thiobutyrate, and 40 mL of ethanol were added to a reaction flask. The temperature was raised to 60 °C for reaction. TLC was used to monitor until there was no Compound I-10. After the reaction was completed, the reaction solution was concentrated, water was added, and it was continuously concentrated until no solvent was distilled out. The concentrate was diluted in 10 times the amount of water, stirred for 30 min, filtered by suction, discharged, and dried to obtain 7.3 g of Compound II-10, with a yield of 89.6% and a purity of 97.2%.

[0110] Example 11

[0111]

[0112] At room temperature, 10 g of Compound I-11, 5.6 g of potassium thiobutyrate, and 50 mL of ethanol were added to a reaction flask. The temperature was raised to 40 °C for reaction. TLC was used to monitor until there was no Compound I-11. After the reaction was completed, the reaction solution was concentrated, water was added, and it was continuously concentrated until no solvent was distilled out. The concentrate was diluted in 10 times the amount of water, stirred for 30 min, filtered by suction, discharged, and dried to obtain 7.1 g of Compound II-11, with a yield of 83.6% and a purity of 95.4%.

[0113] Example 12

[0114]

[0115] At room temperature, 10 g of Compound I-12, 3.5 g of potassium thioacetate and 40 mL of N,N-dimethylformamide were put into a reaction flask, and the temperature was raised to 80 °C for reaction. The reaction was monitored by TLC until there was no Compound I-12. After the reaction was completed, it was diluted in 30 times of water, stirred for 30 min, filtered by suction, discharged, and dried to obtain 7.6 g of Compound II-12, with a yield of 90.7% and a purity of 97.6%.

[0116] Example 13

[0117]

[0118] At room temperature, 10 g of Compound I-13, 2.7 g of potassium thiopropionate and 60 mL of methanol were put into a reaction flask, and the reaction was carried out at 30 °C. The reaction was monitored by TLC until there was no Compound I-13. After the reaction was completed, the reaction solution was concentrated, water was added, and it was continuously concentrated until no solvent was distilled out. The concentrate was diluted in 10 times of water, stirred for 30 min, filtered by suction, discharged, and dried to obtain 6.8 g of Compound II-13, with a yield of 79.5% and a purity of 95.8%.

[0119] Finally, it should be noted that the above examples are only used to illustrate the technical solutions of the present invention and are not intended to limit them; although the present invention has been described in detail with reference to the foregoing examples, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing examples, or perform equivalent replacements on some or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for dehalogenating 9-halogenated steroid compounds, characterized in that, It includes the following steps: Compound I reacts with a thiofatty acid salt to obtain the 9-dehalogenated product Compound II of the 9-halogenated steroid compound, and the reaction formula is as follows: Among them, R1, R2, R3, and R4 shown in the structural formulas of Compound I and Compound II are independently selected from each other, and: R1 = H or methyl; R2 = H, OH or methyl; R3 = H, OH, R5, OR5, OCOR5 or OCOOR5, and R5 is an alkyl group with six or fewer carbon atoms; Or, R2, That is, there is also an oxygen bridge connecting between C16 and C17, and R6 and R7 are each independently H or an alkyl group having six or fewer carbon atoms; Or, R2, That is, there is also an epoxy connection between C16 and C17; Or, R2 and R3 are a single bond, that is, there is also a double bond between the C16 and C17 positions; R4 = CH2R8, R8 = H, OH or OCOR9, and R9 is an alkyl group with six or fewer carbon atoms; X = Cl, Br or I; The dotted line is a single bond or a double bond, The thiofatty acid salt is selected from one or a combination of thioacetates, thiopropionates or thiobutyrates.

2. The method for dehalogenating 9-halogenated steroid compounds according to claim 1, characterized in that, It includes the following steps: Compound I reacts with a thiofatty acid salt to obtain the 9-dehalogenated product Compound II of the 9-halogenated steroid compound, and the reaction formula is as follows: Among them, R1, R2, R3, and R4 shown in the structural formulas of Compound I and Compound II are independently selected from each other, and: R1 = H or methyl; R2 = H or methyl; R3 = H or OH; Or, R2, That is, there is also an oxygen bridge connecting between C16 and C17, and R6 and R7 are each independently H or an alkyl group having six or fewer carbon atoms; or, R2, that is, there is also an epoxy connection between C16 and C17; Or, R2 and R3 are a single bond, that is, there is also a double bond between the C16 and C17 positions; R4 = CH2R8, R8 = H, OH or OCOR9, and R9 is an alkyl group with six or fewer carbon atoms; X = Cl, Br; The dotted line is a single bond or a double bond.

3. The method for dehalogenating 9-halogenated steroid compounds according to claim 1 or 2, characterized in that, It includes the following steps: Compound I reacts with a thiofatty acid salt to obtain the 9-dehalogenated product Compound II of the 9-halogenated steroid compound, and the reaction formula is as follows: Among them, R1, R2, R3, and R4 shown in the structural formulas of Compound I and Compound II are independently selected from each other, and: R1 = H; R2 = H or methyl; R3 = H or OH; R4 = CH2R8, R8 = H or OCOCH3; X = Br; The dotted line is a single bond or a double bond.

4. The method for dehalogenating 9-halogenated steroid compounds according to claim 1, characterized in that, The thioacetate is selected from sodium thioacetate and / or potassium thioacetate; And / or, the thiopropionate is selected from sodium thiopropionate and / or potassium thiopropionate; And / or, the thiobutyrate is selected from sodium thiobutyrate and / or potassium thiobutyrate.

5. The method for dehalogenating 9-halogenated steroid compounds according to any one of claims 1, 2 or 4, characterized in that,In the reaction, the molar ratio of the thiofatty acid salt to Compound I is (1.2 - 2):

1.

6. The dehalogenation method of the 9-halogenated steroid compound according to claim 5, characterized in that, It includes the following steps: Add Compound I and the thiofatty acid salt to a solvent and react at 30 - 80 °C to obtain the 9-dehalogenated product Compound II of the 9-halogenated steroid compound.

7. The dehalogenation method of the 9-halogenated steroid compound according to claim 6, characterized in that, The solvent is selected from one or a combination of C1-C4 alcohols, acetonitrile or N,N-dimethylformamide.

8. The dehalogenation method of the 9-halogenated steroid compound according to claim 6 or 7, characterized in that, The volume-weight ratio of the solvent to Compound I is (3 - 6) mL / g.

9. The application of the dehalogenation method of the 9-halogenated steroid compound according to any one of claims 1-8 in the preparation of corticosteroid drugs and their intermediates.

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